From the Guidelines
Tranexamic acid works by inhibiting plasminogen activation, thus inhibiting fibrinolysis, as a synthetic derivative of the amino acid lysine. This mechanism is crucial in understanding its role in reducing bleeding in various surgical settings, including cardiac and major non-cardiac surgery, major trauma, and postpartum haemorrhage 1. The process involves the competitive binding of tranexamic acid to lysine receptor sites on plasminogen, preventing its interaction with fibrin and thereby blocking the fibrinolytic pathway. This results in the stabilization of existing clots and the prevention of excessive bleeding, making it particularly effective in situations with accelerated fibrinolysis.
Key aspects of tranexamic acid's mechanism and use include:
- Its synthetic derivation from the amino acid lysine, which allows it to inhibit plasminogen activation 1.
- The inhibition of fibrinolysis, which is critical for reducing bleeding in surgical settings and trauma 1.
- The competitive binding to lysine receptor sites on plasminogen, preventing plasmin formation and subsequent fibrin breakdown.
- Its effectiveness in various clinical scenarios, including surgery, trauma, and postpartum haemorrhage, with a notable reduction in blood loss and transfusion requirements when administered early 1.
The safety profile of tranexamic acid has been extensively studied, with meta-analyses indicating no increased risk of thromboembolic complications associated with its use 1. This evidence supports the general safety of the drug, although it should be used with caution in patients, particularly those with renal impairment due to its primary excretion in the urine. Dosage schedules may vary depending on the clinical indication, as outlined in guidelines such as those provided by the Association of Anaesthetists 1.
From the FDA Drug Label
Tranexamic acid is a synthetic lysine amino acid derivative, which diminishes the dissolution of hemostatic fibrin by plasmin. In the presence of tranexamic acid, the lysine receptor binding sites of plasmin for fibrin are occupied, preventing binding to fibrin monomers, thus preserving and stabilizing fibrin’s matrix structure The antifibrinolytic effects of tranexamic acid are mediated by reversible interactions at multiple binding sites within plasminogen.
The mechanism of tranexamic acid (TXA) is as an antifibrinolytic agent, which works by:
- Occupying the lysine receptor binding sites of plasmin for fibrin, preventing binding to fibrin monomers
- Preserving and stabilizing fibrin's matrix structure
- Mediating reversible interactions at multiple binding sites within plasminogen 2
From the Research
Mechanism of TXA
- TXA is an antifibrinolytic agent that exerts its action on the coagulation process by competitively inhibiting plasminogen activation, thereby reducing conversion of plasminogen into plasmin 3, 4.
- This ultimately prevents fibrinolysis and reduces hemorrhage, making TXA well suited for the management of traumatic hemorrhage in the prehospital setting 3.
- TXA binds plasminogen and prevents its maturation to the fibrinolytic enzyme plasmin, which is essential for its antifibrinolytic activity 5.
- Besides preventing fibrinolysis and blood loss, TXA has been reported to suppress posttraumatic inflammation and edema, and has anti-inflammatory activity, protection of the endothelial and epithelial monolayers, stimulation of mitochondrial respiration, and suppression of melanogenesis 5.
Key Findings
- The literature supports the use of a loading dose of 1 g of TXA, followed by 1 g infusion over 8 h, given by intravenous administration within a 3-h window period of traumatic injury 3.
- TXA is very effective and safe to use in the prehospital setting, and its use is clinically and economically feasible 3, 4.
- TXA reduces mortality in patients suffering from trauma and postpartum hemorrhage, and has well-documented beneficial effects in many clinical indications 6.
- However, there is no consensus regarding the optimal TXA dose, and certain dosages and indications can cause harm, such as an increased risk of seizures after high TXA doses with brain injury and cardiac surgery 6, 7.